Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.

Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

“Zinc overload” has emerged as a promising strategy in tumor nanomedicine, wherein exogenous modulation of metal ion homeostasis selectively triggers cancer cell death. Among various bioactive ions, zinc (Zn²⁺) stands out due to its unique ability to simultaneously disrupt energy metabolism, damage mitochondria, degrade mutant p53, and activate antitumor immunity. Notably, tumor cells exhibit greater sensitivity to Zn²⁺ overload while normal cells maintain higher tolerance. This review systematically summarizes design strategies for achieving “zinc overload” using biodegradable zinc-based nanomaterials, focusing on two fundamental questions: how to specifically deliver Zn²⁺ to tumors (targeted delivery), and how to trigger controlled release at the tumor site (release strategies). Current challenges are critically analyzed and future perspectives are offered. For targeted delivery, the strategies are categorized into passive, active, and biomimetic approaches. Passive targeting relies on the enhanced permeability and retention (EPR) effect but suffers from poor enrichment efficiency and rapid clearance. Active targeting conjugates ligands (e.g., folic acid, hyaluronic acid) to recognize overexpressed receptors, significantly enhancing cellular uptake. It is emphasized that hyaluronic acid-modified ZIF-8 can co-deliver siRNA for GLUT1 silencing, achieving systematic energy exhaustion. Biomimetic delivery using cell membranes confers immune evasion, prolonged circulation, and homologous targeting, exhibiting the lowest off-target toxicity. This approach is considered to guide future nanocarrier design. For Zn²⁺ release, 4 mechanisms are discussed. Endogenous environment-responsive release exploits acidic pH to degrade materials like ZIF-8 or ZnO, causing mitochondrial dysfunction, reactive oxygen species (ROS) burst, and autophagic blockade. Incorporation of other ions (Ca²⁺, Mn²⁺, Ni²⁺) enables synergistic metabolic interference and immune activation. Exogenous responsive release using near-infrared light offers spatiotemporally precise activation. For example, a nanorobot combining black phosphorus with ZIF-8 accelerates Zn²⁺ release under dual acid and light stimuli. Ion exchange represents an elegant trigger: zinc complexes (e.g., Zn-carnosine) have higher affinity for Cu²⁺; competitive coordination releases Zn²⁺ while depleting Cu²⁺, dually inhibiting oxidative phosphorylation and glycolysis. This mechanism is proposed to hold promise for overcoming metabolic reprogramming. Finally, biological regulation—silencing the ZnT1 zinc transporter to block Zn²⁺ efflux—represents a paradigm shift from passive delivery to active homeostatic disruption. This “block and attack” strategy may prevent acquired resistance. The therapeutic consequences of zinc overload are multifaceted. Zn²⁺ causes lysosomal membrane permeabilization and impaired SNARE complex formation, blocking autophagic flux and inducing a distinct cell death termed “zincosis”. In mitochondria, Zn²⁺ inhibits glutathione reductase, causing oxidative stress and electron transport chain blockade. Meanwhile, Zn²⁺ suppresses glycolytic enzymes (GAPDH, LDHA), leading to ATP depletion and reversing drug resistance by downregulating P-glycoprotein. Moreover, zinc overload triggers immunogenic cell death, promoting dendritic cell maturation and CD8⁺ T cell infiltration. Combined with cGAS-STING activation, this reshapes the immunosuppressive tumor microenvironment and inhibits distant metastasis. These interconnected mechanisms endow zinc overload with a unique advantage over single-modality treatments. Despite remarkable preclinical efficacy, challenges remain: systemic toxicity from off-target release, potential zinc tolerance via metallothionein upregulation, and insufficient pharmacokinetic data. Future directions should prioritize: (1) intelligent stimuli-responsive materials; (2) combination with immune checkpoint inhibitors;(3) theragnostic integration; (4) deeper mechanistic studies; and (5) artificial intelligence-assisted screening. Zinc overload therapy is expected to become an indispensable component of integrated tumor treatment.

Perforin 2(MPEG 1)is a member of the MACPF(membrane attack complex/PRF membrane attack complex/perforin)superfamily,which is mainly secreted by cytotoxic T lymphocytes,natural killer cells and mac-rophages Through the formation of active pores on the target cell membrane,perforin 2 participates in altering the permeability-pressure of the target cell,or collaborates with granzymes to induce the apoptosis of target cells.Re-cently,with the development of molecular biology,MPEG 1 has been increasingly studied,and the unique gene se-quence and cell types of perforin 2 have specific functions and adaptive evolution in different immune cells,which may determine its performance and therapeutic potential in different disease states.

Objective To observe the feasibility and accuracy of simplified prenatal ultrasonic evaluation on fetal bilateral lateral fissures.Methods A total of 513 pregnant women with gestational ages ranging from 20-34 weeks were prospectively enrolled.Transabdominal ultrasound screening of fetal bilateral lateral ventricular fissures on the transforaminal plane were performed,the ultrasonic display rate and characteristics like morphology of bilateral lateral fissures were recorded,and a simple grading system(3 levels)was applied for evaluating the fissures.Fetuses with abnormalities were further examined with MR,amniotic fluid/cord blood tests or whole-exome sequencing of umbilical cord tissue after birth.The pregnancy outcomes were documented.Results Normal fetal bilateral lateral fissures were observed using simplified prenatal ultrasonic evaluation in 500 fetuses whom were then successfully delivered,and normal cortical development was found in these 500 newborns,while abnormalities were detected in 13 fetuses.The display rate of transabdominal ultrasound on transforaminal plane for fetal bilateral lateral ventricular fissures was 92.20％(473/513).From 20 to 34 weeks,the morphology of bilateral lateral fissures could be simply graded into 3 levels:Level 1 presented as a shallow arc shape from 20-22 weeks,Level 2 presented as a blunt or right-angled broad platform from 22-26 weeks,and Level 3 presented as an acute-angled broad platform from 25-34 weeks.In 500 fetuses with normal development,the morphology of the near-field lateral fissures consistently developed in parallel with the far-field lateral fissures as gestational age increased.Among 13 fetuses with abnormal findings,abnormalities of bilateral lateral fissures were found in 8 fetuses,while unilateral abnormality was noticed in 5 fetuses.MR examination of all 13 fetuses and amniotic fluid whole-genome sequencing of 9 fetuses indicated abnormal cortical development.Conclusion Simplified prenatal ultrasound based on transforaminal column cross-section could conveniently and accurately classify morphology of fetal bilateral lateral sulcus.

Objective:To evaluate the efficacy of dexzopiclone combined with repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders (PSSD) and its effects on sleep electroencephalography and neuroelectrophysiological parameters.Methods:180 PSSD patients admitted to Yulin First Hospital (December 2019-December 2020) were randomized into medication group ( n=90, dexzopiclone) and rTMS group ( n=90, dexzopiclone+rTMS). Outcomes included clinical efficacy, sleep quality [Pittsburgh Sleep Quality Index (PSQI), Self-Rating Scale for Sleep (SRSS)], electroencephalogram parameters [sleep latency (SL), total sleep time (TST), sleep efficiency], neuroelectrophysiological indices [bilateral motor thresholds], biochemical markers [S100β protein, brain-derived neurotrophic factor (BDNF)], adverse reactions, and 1-year recurrence rate. Results:After treatment, the rTMS group had a significantly higher efficacy (92.22%, 83/90) compared to the medication group (81.11%, 73/90) ( χ2=4.81, P=0.028). Compared to post-treatment, PSQI decreased to [7.47 (6.63,8.69) points vs. 13.56 (3.15,19.51) points] in the rTMS group and [9.56 (8.59,11.11) points vs. 14.01 (2.58,20.55) points] in the medication group ( U=8.82, 8.38; both P<0.001). SRSS scores decreased to [(15.23±2.88) points vs. (28.81±4.99) points) ( t=32.74, P<0.001) and (19.54±3.59) points vs. (28.15±4.71) points) ( t=19.68, P<0.001)], respectively. Compared to before treatment, the rTMS group had lower scores than the medication group ( U=7.80, t=8.88; P<0.01). SL reduced to (27.65±5.12) min vs. (44.92±8.21) min ( t=24.58, P<0.001) in rTMS group and (38.78±6.34) min vs. (45.23±8.56) min ( t=8.24, P<0.001) in medication groups. TST increased to (348.50±56.27) min vs. (299.21±52.14) min ( t=8.63, P<0.001) and (311.42±55.39) min vs. (275.65±52.23) min ( t=6.31, P<0.001), sleep efficiency improved to (70.96±12.33%) vs. (57.43±10.98%) ( t=11.01, P<0.001) and (62.37±11.28%) vs. (56.78±10.72%) ( t=4.82, P<0.001), while the rTMS group showed greater improvement ( t=4.46, 4.88; P<0.001). Compared to before treatment, left motor thresholds decreased to (55.65±2.48)% vs. (64.37±3.12)% and (61.76±3.17)% vs. (65.12±3.45)% post-treatment ( t=29.54, 9.63; P<0.001), with significant intergroup differences ( t=14.40, P<0.001). Right motor thresholds decreased to (56.28±3.45)% vs. (67.42±3.61)% and (60.89±3.39)% vs. (66.62±3.54)% ( t=29.94, 15.69; P<0.001), with intergroup differences ( t=9.04, P<0.01). Compared to before treatment, serum S100β levels decreased in both group post-treatment (23.65±3.23) ng/L vs. (65.37±7.89) ng/L and (29.76±3.61) ng/L vs. (63.48±7.34) ng/L ( t=71.19, 58.43; P<0.001), with lower levels in the rTMS group ( t=11.97, P<0.001). Compared to before treatment, BDNF increased to (554.48±69.78) ng/L vs. (502.82±64.11) ng/L and (524.90±67.66) ng/L vs. (505.12±64.45) ng/L post-treatment ( t=7.32, 2.84; P=0.001, 0.030), with higher levels in the rTMS group ( t=2.89, P=0.004). Adverse reaction rates were 4.44% (4/90) and 3.33% (3/90), respectively ( χ2=0.15, P=0.700). Recurrence rates were 1.18% (1/85) in the rTMS group and 3.90% (3/77) in the medication group ( χ2=0.37, P=0.544). Conclusion:The combination of dexzopiclone and repetitive transcranial magnetic stimulation (rTMS) demonstrates significant advantages and efficacy in treating post-stroke sleep disorders (PSSD). This approach comprehensively improves patients' sleep quality, EEG parameters and neuroelectrophysiological indicators while enhancing the regulatory effects of brain-derived neurotrophic factor (BDNF). Additionally, the therapy exhibits a favorable safety profile and prognosis.

Objective:To analyze the results of prenatal diagnosis for fetuses with a high risk for sex chromosome aneuploidies (SCAs) indicated by non-invasive prenatal testing (NIPT), and to assess the influence of maternal chromosomal factors on the results of NIPT.Methods:A retrospective analysis was conducted on the clinical data of 454 pregnant women with a high risk for SCAs indicated by NIPT undergoing invasive prenatal diagnosis at the Medical Genetics Center of Northwest Women′s and Children′s Hospital from January 2022 to September 2024. The data has included prenatal diagnosis indications, results, pregnancy outcomes, and chromosomal results of the pregnant women. This study has been approved by the Ethics Committe of Northwest Women′s and Children′s Hospital(Ethics No.2024-132)Results:Among the 454 women (including 10 with twin pregnancy) with a high risk for SCAs indicated by NIPT, 149 (including 4 twin cases) were diagnosed with SCAs through invasive prenatal diagnosis. These had included 47, XXX (37 cases), 47, XXY (56 cases), 47, XYY (29 cases), 45, X (1 case), 48, XXYY (1 case), mosaicism (20 cases), sex chromosome structural abnormalities (6 cases), and small-scale pathogenic copy number variations (3 cases). 383 pregnant women (including 7 with twin pregnancy) had accepted chromosomal karyotyping analysis. In total 49 cases(including 1 twih case) of SCAs were detected. Among them, 41 cases were pregnant women with SCAs but normal fetal chromosomes, which yielded a false positive rate for NIPT caused by maternal factors by 10.7%. In addition, 9 cases (including 1 twin case) had SCAs in both the pregnant woman and the fetus. Among the 383 pregnant women, 129 cases (including 3 twin cases) of fetal SCAs were diagnosed, which yielded an overall positive predictive value (PPV) of NIPT for SCAs by 33.7% (129/383). With the 41 false positive cases caused by maternal SCAs excluded, the PPV of NIPT for SCAs will be increased to 37.7% (129/342). Among the 454 pregnant women, twin pregnancies have accounted for 2.2% (10/454). Among the confirmed cases of SCAs, twin cases accounted for 2.7% (4/149). Among the 383 pregnant women undergoing chromosomal karyotyping, twin cases accounted for 1.8% (7/383). Among the detected cases of chromosomal abnormalities, twin cases accounted for 2.0% (1/49). Among singleton pregnancies, the positive predictive value (PPV) of NIPT for sex chromosome aneuploidies (SCAs) was 32.7% (145/444), in twin pregnancies, the PPV was 40.0% (4/10).Conclusion:NIPT can improve the screening efficiency for SCAs, but its PPV is limited. Therefore, pregnant women with a high risk for SCAs indicated by NIPT need to undergo invasive prenatal diagnosis for a definite diagnosis, while the PPV in twin pregnancies may be higher than in singletons, this observation is limited by the small sample size of twins in our study. The study confirmed that chromosomal abnormalitpies in pregnant women can significantly affect the accuracy of NIPT in detecting fetal SCAs. Therefore, when NIPT indicates SCAs, it is recommended to simultaneously conduct chromosomal karyotyping for the pregnant women. The combined application of chromosomal karyotyping analysis, fluorescence in situ hybridization, and copy number variation detection techniques can significantly improve the diagnostic accuracy for SCAs, especially for the detection of mosaicisms.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
Humans ; Apoptosis/drug effects* ; Hep G2 Cells ; Glycyrrhetinic Acid/pharmacology* ; Doxorubicin/pharmacology* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/physiopathology* ; Mitochondria/metabolism* ; Endoplasmic Reticulum/metabolism* ; Cell Survival/drug effects* ; Membrane Proteins/genetics*